1. Field of the Invention
This invention relates to a process for preparing 4-fluoro-3-trifluoromethylphenol which is a starting material of an agricultural chemical.
2. Prior Art
"4-Fluoro-3-trifluoromethylphenol" (hereinafter also referred to as "the desired compound") is a compound which is useful as a starting material of an agricultural chemical.
For example, N-benzyl-2-(4-fluoro-3-trifluoromethylphenoxy)butanoic acid amide (a compound described in Japanese Provisional Patent Publication No. 10749/1988) which is used as a herbicide is synthesized through the desired compound.
As a process for preparing the desired compound from "4-fluoro-3-trifluoromethylaniline" (hereinafter also referred to as "the starting aniline"), there may be mentioned processes described in (1) Japanese Provisional Patent Publication No. 125245/1976, (2) Japanese Provisional Patent Publication No. 246244/1991, (3) J. Med. Chem., vol. 25, pp. 1097 to 1101 (1982) and (4) Japanese Provisional Patent Publication No. 268658/1989.
Further, as a process for preparing 4-fluorophenol from 4-fluoroaniline which is an analogue of the starting aniline, there may be mentioned a process described in (5) Japanese Provisional Patent Publication No. 316544/1994.
In the publication (5), it is described that a 4-fluorobenzenediazonium salt derived from 4-fluoroaniline has poor heat stability and a fluorine group at 4-position relative to a diazonium group which is an electron attractive group is easily substituted by a hydroxyl group (a defluorination-hydroxylation reaction). However, it is described that a defluorination-hydroxylation reaction does not occur at 15.degree. to 25.degree. C.
However, it could be confirmed that in the case of the starting aniline, a trifluoromethyl group at 3-position relative to a diazonium group further activates a reactivity of a fluorine group at 4-position by a hydroxyl group, whereby a defluorination-hydroxylation reaction at 4-position occurs even at room temperature.
That is, the present inventors have isolated 2-trifluoromethyl-4-diazocyclohexa-2,5-dienone with a yield of 88% showing that a defluorination-hydroxylation reaction proceeds by preparing "a 4-fluoro-3-trifluoromethylbenzenediazonium salt" (hereinafter also referred to as "the diazonium salt"), retaining the diazonium salt at room temperature for 24 hours and then neutralizing it with sodium carbonate according to a method as shown in Reference example 1 described below.
It is considered that the reason why the diazonium salt is extremely unstable in this case is not merely that its stability to temperature is poor but that such a problem is caused by neutralization operation using sodium carbonate.
Even in the case of a method in which the diazonium salt is retained at 0.degree. to 5.degree. C. at which better temperature stability is given as compared with retention at room temperature as shown in Comparative example 5 described below, an amount of the desired compound is reduced by 42% after 24 hours.
From these two facts, it can be seen that a main side reaction is a defluorination-hydroxylation reaction of the diazonium salt due to heat.
Also, from a result of preparing the diazonium salt by the process described in the publication (4) and examining the stability of the diazonium salt at 0.degree. C., it has been found that the same by-product as described above is produced with the lapse of time (it was produced by about 15% in 24 hours) to lower the yield of the desired compound.
Therefore, it has been clarified that when the diazonium salt is prepared from the starting aniline under preparation conditions of 4-fluoro-3-trifluoromethylphenol described in the publication (4), there is a problem that the yield of the diazonium salt is lowered by a side reaction in which fluorine at 4-position is subjected to a defluorination-hydroxylation reaction, whereby lowering of the yield of the desired compound is brought about.
From the foregoing, it has been found that in order to heighten the yield of the desired compound, it is extremely important to heighten the stability of the diazonium salt.
Incidentally, in the above publications and literature (1) to (4), the desired compound can be obtained through the respective steps of preparing "sulfate of the starting aniline" (hereinafter also referred to as "the starting aniline sulfate"), diazotizing the starting aniline sulfate and hydrolyzing the resulting diazonium salt. It has been considered that the diazotization reaction step is an exothermic reaction accompanied with high heat and the produced diazonium salt has poor heat stability so that a method of effecting a diazotization reaction at 0.degree. to 10.degree. C. has been used.
However, a time required for preparing the desired compound on an industrial level is much longer than a time required on an experimental level as in the above publications and literature (1) to (4).
This fact means that lowering of the yield of the desired compound is brought about in industrial production.
Incidentally, one of the important factors for reducing fixed cost in industrial production of the desired compound is to heighten a substrate concentration in order to heighten productivity.
Although the diazonium salt concentrations described in the publications (1) and (2) are high, an isolation yield is as low as 52% in the publication (1), and it is described in the publication (2) that the desired compound was obtained with a yield of 85%, but the desired compound could be obtained only with a reaction yield of 25% in a tracing experiment by the present inventors.
In tracing experiments of the literature (3) and the publication (4) by the present inventors, it could be confirmed that the desired compound could be obtained with a high yield and a yield at 0.degree. C. after 24 hours of the literature (3) is not decreased, but productivity was poor due to a low diazonium salt concentration.
The desired compound is obtained through the steps of preparing sulfate of the starting aniline, diazotizing the sulfate and hydrolyzing the resulting diazonium salt.
Therefore, in the case where a substrate concentration is heightened, in the step of preparing the starting aniline (an exothermic reaction), such a fear that the starting aniline sulfate is precipitated (scaling) in a reaction tank during cooling to the temperature (0.degree. to 5.degree. C.) of a diazotization reaction, and a thermal conductivity coefficient is lowered to worsen a cooling effect is increased. Further, the diazotization reaction is an exothermic reaction so that a diazotizing agent is reacted under cooling. When excessive cooling is effected, a part of the starting aniline sulfate which has been dissolved is reprecipitated, and further, inorganic substances such as sodium sulfate are precipitated, whereby a cooling efficiency is worsened.
As temperature is controlled strictly so that excessive cooling is not effected in order to avoid such a fear, a time required for adding a diazotizing agent is elongated.
Thus, when a substrate concentration is heightened, long and strict temperature control is required, and various troubles are liable to be caused.
Due to the troubles, the yield of the desired compound is lowered.
As described above, in the above publications and literature (1) to (4), processes for preparing the desired compound are described, but it is not disclosed that the yield of the desired compound greatly depends on the stability of the diazonium salt in a process for preparing the desired compound on an industrial scale.
That is, in the above publications and literature (1) to (4), it is not disclosed that the stability of the diazonium salt is intended to be heightened and the desired compound can be obtained with a high yield by using the diazonium salt retained at a high concentration.